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Nutrient-Deprived Retinal Progenitors Proliferate in Response to Hypoxia: Interaction of the HIF-1 and mTOR Pathway

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK
Authors to whom correspondence should be addressed.
Academic Editors: Benjamin Yat-Ming Yung and Simon J. Conway
J. Dev. Biol. 2016, 4(2), 17;
Received: 15 March 2016 / Revised: 12 May 2016 / Accepted: 13 May 2016 / Published: 19 May 2016
(This article belongs to the Special Issue Developmental Mechanisms in Tumorigenesis)
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At a cellular level, nutrients are sensed by the mechanistic Target of Rapamycin (mTOR). The response of cells to hypoxia is regulated via action of the oxygen sensor Hypoxia-Inducible Factor 1 (HIF-1). During development, injury and disease, tissues might face conditions of both low nutrient supply and low oxygen, yet it is not clear how cells adapt to both nutrient restriction and hypoxia, or how mTOR and HIF-1 interact in such conditions. Here we explore this question in vivo with respect to cell proliferation using the ciliary marginal zone (CMZ) of Xenopus. We found that both nutrient-deprivation and hypoxia cause retinal progenitors to decrease their proliferation, yet when nutrient-deprived progenitors are exposed to hypoxia there is an unexpected rise in cell proliferation. This increase, mediated by HIF-1 signalling, is dependent on glutaminolysis and reactivation of the mTOR pathway. We discuss how these findings in non-transformed tissue may also shed light on the ability of cancer cells in poorly vascularised solid tumours to proliferate. View Full-Text
Keywords: neural progenitors; hypoxia; nutrition; proliferation neural progenitors; hypoxia; nutrition; proliferation

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Khaliullina, H.; Love, N.K.; Harris, W.A. Nutrient-Deprived Retinal Progenitors Proliferate in Response to Hypoxia: Interaction of the HIF-1 and mTOR Pathway. J. Dev. Biol. 2016, 4, 17.

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